Project Summary/Abstract The CDC recently declared insufficient sleep to be a ?public health epidemic,? noting that an estimated 50-70 million US adults have sleep or wakefulness disorders. Although it is well-recognized that insufficient sleep increases the risk for many chronic conditions, the role of sleep in the development of cancer is unclear. While epidemiologic studies are sparse, they have yielded some provocative but inconsistent findings. Such inconsistencies may reflect the complexity of underlying etiologic mechanisms. Sleep plays a fundamental role in the maintenance of a number of key processes integral to carcinogenesis, including inflammation and cellular replication and proliferation. Furthermore, there may be individual differences in vulnerability to the effects of sleep deficiency, depending on chronotype (i.e., whether one?s endogenous biological rhythm of sleep/wakefulness follows a morning or evening preference). Our objective is to advance the understanding of how sleep deficiency may influence cancer risk, considering both potential underlying mechanisms and host vulnerability. The study will capitalize on resources available from the California Teachers Study (CTS) in which 65,000 women have provided detailed self-reported data on sleep and chronotype, a subset of whom have also provided blood samples available for the conduct of biomarker assays to quantify physiologic effects. The specific aims are to: 1.) evaluate cancer risks associated with self-reported sleep deficiency among CTS participants; 2.) assess the relationship between self-reported sleep deficiency and biomarkers of physiologic effect for chronic inflammation and telomere length; 3.) evaluate the degree to which cancer risks and the physiologic responses to sleep deficiency vary by chronotype. In addressing each of these aims, several specific dimensions of sleep deficiency will be considered, including poor sleep quality, extremes in sleep duration, fragmented sleep and long sleep latency. Cases of invasive breast and other selected commonly-diagnosed cancers (colorectal, melanoma, endometrial, non-Hodgkin?s lymphoma, thyroid) will be identified via linkage to the California Cancer Registry. Biomarker assays will be run on 800 blood samples collected from non- cancer cases within a year of the sleep and chronotype data. Multiplexed immunometric assays will be used to quantify levels of circulating biomarkers of inflammation. Quantitative PCR will be used to measure telomere length. Cox Proportional Hazards and Ordinary Logistic Regression models will be used to estimate risks for each dimension of sleep deficiency, adjusting for other known risk factors. Multivariable linear models will be used to characterize the relationship between the biomarkers and specific dimensions of sleep. Initial models will be expanded, incorporating chronotype to explore potential differences in risk and/or effect by chronotype. The long-term objective of this project supports the NCI?s mission to reduce the burden of cancer by furthering our understanding of its etiology and avenues for prevention. Additionally, it supports NIH?s recently identified priority to advance the understanding of sleep and circadian functions in health and disease.